title: Are interstitial cells of Cajal involved in mechanical stress-induced gene expression and impairment of smooth muscle contractility in bowel obstruction?
abstract: OBJECTIVE
  The network of interstitial cells of Cajal (ICC) is altered in obstructive bowel disorders (OBD). However, whether alteration in ICC network is a cause or consequence of OBD remains unknown. This study tested the hypothesis that mechanical dilation in obstruction disrupts the ICC network and that ICC do not mediate mechanotranscription of COX-2 and impairment of smooth muscle contractility in obstruction.
  
  
  METHODS
  Medical-grade silicon bands were wrapped around the distal colon to induce partial obstruction in wild-type and ICC deficient (W/W(v)) mice.
  
  
  RESULTS
  In wild-type mice, colon obstruction led to time-dependent alterations of the ICC network in the proximal colon segment. Although unaffected on days 1 and 3, the ICC density decreased markedly and the network was disrupted on day 7 of obstruction. COX-2 expression increased, and circular muscle contractility decreased significantly in the segment proximal to obstruction. In W/W(v) control mice, COX-2 mRNA level was 4.0 (±1.1)-fold higher (n=4) and circular muscle contractility was lower than in wild-type control mice. Obstruction further increased COX-2 mRNA level in W/W(v) mice to 7.2 (±1.0)-fold vs. W/W(v) controls [28.8 (±4.1)-fold vs. wild-type controls] on day 3. Obstruction further suppressed smooth muscle contractility in W/W(v) mice. However, daily administration of COX-2 inhibitor NS-398 significantly improved muscle contractility in both W/W(v) sham and obstruction mice.
  
  
  CONCLUSIONS
  Lumen dilation disrupts the ICC network. ICC deficiency has limited effect on stretch-induced expression of COX-2 and suppression of smooth muscle contractility in obstruction. Rather, stretch-induced COX-2 plays a critical role in motility dysfunction in partial colon obstruction.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Chester C
authors.initials: CC
authors.lastname: Wu
authors.forename: You-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Jerry
authors.initials: J
authors.lastname: Gao
authors.forename: John H
authors.initials: JH
authors.lastname: Winston
authors.forename: Leo K
authors.initials: LK
authors.lastname: Cheng
authors.forename: Xuan-Zheng
authors.initials: XZ
authors.lastname: Shi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D056885:Interstitial Cells of Cajal / Q000502:physiology*; D007415:Intestinal Obstruction / Q000378:metabolism*; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009578:Nitrobenzenes / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2